Clinical benefit of apitegromab sustained for up to 3 years: Study
Motor function improved for patients in TOPAZ extension trial
Three years of treatment with apitegromab, a muscle-targeting therapy being developed by Scholar Rock, continues to provide clinical benefit to children and young adults with spinal muscular atrophy (SMA) type 2 or 3 who are not able to walk.
That’s according to long-term results from the open-label extension of the Phase 2 TOPAZ (NCT03921528) study.
“Results of the TOPAZ study at 36 months reinforce the longer-term benefit of apitegromab treatment in patients with SMA, with continued and sustained improvement across both clinical and caregiver-reported outcomes,” the researchers wrote.
The study, “Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study,” was published in Frontiers in Neurology.
In SMA, the nerve cells that control the body’s movements, called motor neurons, begin to die, causing muscle weakness. SMA type 2 typically appears in infancy, and children may not gain the ability to stand or walk, whereas SMA type 3 appears later in childhood, and the ability to walk independently may be lost.
Blocking inactive protein
Apitegromab is an antibody designed to block the inactive form of myostatin, a protein that limits muscle growth and repair. By preventing myostatin from becoming active, apitegromab is expected to increase muscle mass and improve motor function.
The TOPAZ study evaluated apitegromab’s safety and efficacy as an additional or single therapy in 58 children and young adults, ages 2 to 21, with SMA type 2 or 3. Participants were divided into three groups based on disease type and/or ability to walk. Most were also were being treated with Biogen’s Spinraza (nusinersen).
Apitegromab was administered at 2 mg/kg or 20 mg/kg via infusion into the bloodstream every four weeks for up to one year. All 57 patients who completed the study joined its open-label extension, where they received the higher dose for up to three years.
Consistent with two-year results from non-ambulatory patients(those who could not walk), which showed that motor function continued stable or improved after another year on apitegromab, the treatment continued to bring clinical benefit for up to three years.
Among 35 non-ambulatory patients, with a mean age of 7.3, there was an average increase of four points in a standardized measure of motor function called the Hammersmith Functional Motor Scale Expanded (HFMSE), on which a higher score indicates better motor function.
Over the same time window of three years, Revised Upper Limb Module (RULM) scores increased by an average 2.4 points, indicating better motor function in the hands and arms. This analysis excluded seven patients who had surgery for scoliosis, or an abnormally curved spine.
After three years of treatment, most patients (88%) had maintained or improved their World Health Organization motor milestones compared with the study’s start. Of 20 patients who had started treatment with Spinraza before age 5, six achieved new motor milestones, including two who were able to walk independently.
Caregivers also reported improvements in daily activities such as getting dressed or eating, and an easing of fatigue, “a commonly reported symptom in patients living with SMA,” the researchers wrote.
The safety profile of apitegromab was consistent with what was observed during the initial one-year study, with no new safety concerns arising. The most common side effects included fever (48.6%), common cold (45.7%), vomiting (40%), COVID-19 infection (40.0%) and upper respiratory tract infection (31.4%).
“These findings support further development of apitegromab,” the researchers concluded, noting that the ongoing Phase 3 SAPPHIRE study (NCT05156320) will further test apitegromab’s safety as an add-on therapy to Spinraza and Evrysdi (risdiplam).
About the Author
